first in human study: lis1, an induction treatment in kidney transplanted patients

Conditions: Kidney Transplant

Summary: this first in human study aims at evaluating lis1, a stabilized solution of purified anti-t lymphocytes polyclonal glyco-humanized swine igg with immunosuppressive activity, in regards of safety, t cell depletion, and pharmacokinetics / pharmacodynamics in 10 kidney transplant recipients.


Eligibility criteria:
inclusion criteria: * participants must be listed for kidney transplantation, * ad cohort participants: first transplantation, panel reactive antibody (pra) \< 20%, negative donor specific antibody (dsa), no anti-hla antibodies, epstein-barr virus positive (ebv+) serology, * td cohort participants: first transplantation, 0-50 % pra, negative dsa, negative flow cytometry crossmatch (fcxm) for any patients with anti-hla antibodies on screening is mandatory, epstein-barr virus positive (ebv+) serology * participants must weigh at least 50 kg and have a body mass index (bmi) 18.0 ≤ bmi \< 35.0 kg/m2, * white blood cells \> 3000/mm3, platelets \> 75000/mm3, * female participants (wocbp) must have a negative pregnancy test at screening and use a highly effective birth control until 90 days after the last administration of study drug, * non-vasectomized male subjects having a female partner of childbearing potential must agree to the use of a highly effective method of contraception until 90 days after the last administration of study drug, * participants must be capable of giving signed informed consent. exclusion criteria: * patients with an active cancer or a history of kidney cancer, * patients who have previously been exposed to other anti-lymphocyte globulins, * patients with previous organ transplantation, * patients with a history of specific viral infection that would contraindicate depleting antibody therapy (hepatitis b and c, hiv), * patients with a positive hiv and/or hepatitis b and c tests * patients who have uncontrolled concomitant bacterial or viral infections (unresolved during screening), mycosis and/or parasitosis, * patients with a significant liver function impairment: enzyme (ast and/or alt) values must not exceed 1.5 times upper limit of normal, * patients with positive testing for tuberculosis (using quantiferon-tb test), patients with cmv d+/r- constellation at transplant, * patients with seronegative ebv prior to transplantation, * patients who have previously been exposed to antibodies of swine origin, * expanded criteria donor (ecd) defined as donor older than 60 years, * participants who have participated in another research study involving an investigational product in the previous 3 months, * patients with cardiovascular or severe respiratory comorbidities (severe chronic respiratory failure, severe pulmonary fibrosis, obesity-ventilation syndrome, severe idiopathic pulmonary arterial hypertension) not allowing general anesthesia, * patients with type 1 diabetes, * participants who are pregnant, breast feeding or planning pregnancy during the study, * participants who have any form of substance abuse (drug, alcohol...), any other health abnormalities (psychiatric disorders) or condition that according to the investigator's opinion might endanger patient during his/her participation in the study.

Keywords: immunosuppression polyclonal igg allograft transplantation induction treatment acute graft rejection